Process of making the esters of polynuclear hydroxyketones



Patented July 11, 1939 um-m);

I G 'rnnns'rnnsor POLYNUCLEAR HYDROXYKETONES Leopold Ruzicka, Zurich,: Switzerland, assignor 1 to firm of Society of Chemical Industry inBasle,

Basel, Switzerland No Drawing. Application October 26;1935, Serial No. 46,966. In Switzerland Novemberfi, 193

6 Claims. (01. 2604 397 f In specification Ser. No. 747,989, filed October 11, 1934, is described a manufacture of polynuclear cyclic ketones from sterols or bile acids containing saturated ring systems, or from their derivatives or partial degradation products. The manufacture described in the saidspecification comprises treating with an oxidizing agent a derivative of the sterol or bile acid in which the hydroxyl-groups in the nucleus have been protected against direct oxidation, for instance by substitution of their hydrogen atoms, such as by the formation of esters, or by replacement of the hydroxyl-groups by halogen. From the reaction mass resulting from the oxidation the neutral portions are separated, the volatile reaction products are expelled and the cyclic ketones contained in the non-volatile portions are separated by means of ketone reagents, if desired after previous distillation, and the products so obtained are treated with anagent having an hydrolytic action.

Esters of the hydroxyketones obtainable by the aforesaid manufacture are of particular interest. They can be obtained by esterification of the hydroxyketones themselves. They are also formed intermediately during the hydrolysis of the reaction products obtained in the aforesaid manufacture by the action of a ketone reagent on the hydroxyketones esterified in the hydroxylgroups. However, when the hydrolysis occurs under energetic conditions, the ester-groups which are present are wholly or in part split off with the formation of the hydroxyketone.

In accordance with the invention the esters may be easily obtained by subjecting the starting materials to a mild hydrolysis, for instance with the aid of a strong acid in the presence of a small proportion of water, and, if required, in the presence of an organic solvent for the reactants, such as for instance an alcohol, glacial acetic acid or mixtures thereof. By such a mild treatment only the residu of the ketone reagent is eliminated Whilst the ester groups remain undecomposed.

The following examples illustrate the invention:-

Example 1 mgs. of the semicarbazone of the acetate of the hydroxyketone resulting from the oxidation of epi-dihydrocholesterin acetate are heated for half-an-hour on a water bath with 2 grams of a solution obtainable by mixing together 9 grams of glacial acetic acid, 1 gram of concentrated sulfuric acid and 1 gram of water. The reaction mixture is then mixed with ice and sodium carbonate and the acetate of the hydroxyketone which is precipitated is extracted with 60 ether. When recrystallized from methyl alcohol it melts at 164165 C. (correctedh It'h'as the.

following formula:

omooo Y r 1 mH/g In a similar manner there is for instance obtained the propionate of the hydroxyketone of melting point 151-152 C. by treating the semicarbazone of the propionate of the above hydroxyketone withisulfuric acid and water in the presence of propionicacid.

Example 2 melts with decomposition at 215 C. (corrected). Alkaline saponiflcation of the benzoate yields the free hydroxyketone which melts at 174-175.5 C. (corrected) y In a quite analogous manner there is also obtained the androsterone benzoate of melting point 178-1785 C. from its semicarbazone or oxime obtained after the oxidation of epi-dihydrocholesterin.

In a similar manner there may also be obtained other aromatic esters for instance the toluic acid esters.

What I claim is: I

1. The process for the production of esters of polynuclear hydroxyketones, comprising subjecting the products of the reaction of ketone reagents on the hydroxyketones of the cyclopentano-polyhydro-dimethyl-phenanthrene series esjecting the products of the reaction of ketone reagents on the hydroxyketones of thecyclopentano-polyhydro-dimethyl-phenanthreneseries esterified at the hydroxyl-group to a mild hydrolysis with sulfuric acid in the presence of a small proportion of water and of an organic solvent for the reactants consisting of ,the .acid .with which the hydroxyketone is esterified.

3. The process for the production of esters of polynuclear hydroxyketones, comprising subjecting the products of the reaction of ketone reagents on the hydroxyketones of the cyclopentanopolyhydro-dimethyl-phenanthrene series esterified at the hydroxyl-group to a mild hydrolysis by treatment with an alcoholic solution of oxalic acid containing a small proportion of water.

4. The process for the production of esters of the fprmulaz by hydrolyzing their reaction products with ketonereagents with sulfuric acid inthe presence of small proportions of water and of acetic acid as a solvent.

5. The process for the production of esters of by hydrolyzing their reaction products with ketone reagents with an alcoholic solution of oxalicacid containing-small proportions of water.

6. Theprocessfor-the production of esters of the -formula:

by hydrolyzing their semicarbazones withan alcoholic solution of oxalic acidcontaining smallproportions of water.

LEOPOLD 'RUZICKA. 

